The overall objective of this program is to devise an accurate and reproducible system for the determination of glycosylated hemoglobin and in addition to define and develop a variety of techniques for the evaluation of the retinal circulatory dynamics and retinal diffusion function. A high pressure liquid chromatography system for the accurate and reproducible determination of hemoglobin AIc has been perfected. A novel computerized microdensitometric system has been developed for the accurate measurement of density of fluorescein obtained on fluorescein angiograms for calculations of retinal circulation times. The degree of accuracy has been defined and is satisfactory for clinical investigative purposes. A clinical reproducibility study has been designed to evaluate the influence of lapsed time (1 day to 1 week) upon fluorescein angiograms and in addition to define the influence, if any, of meals upon the retinal circulation. An optical system has been assembled for the measurement of fluorescein into the vitreous of the eye. A number of important modifications to this basic measurement have been made. Currently, a survey of the magnitude of fluorescein leakage is being conducted to determine the range of readings in various anatomical locations within the eye in a large group of healthy normal volunteers and in diabetic patients with no evidence of retinopathy and in diabetic patients with evidence of retinopathy.